Quiz 9 Flashcards
classes of lipid
- fatty acids [precursors, lipid tails, detergents]
- triacylglycerols [storage]
- glycerophospholipid [ membrane structures ]
- sphingolipids [ membrane structures ]
- isoprene-based lipids including steroids: cholesterol & hormones
- waxes
saturated
- single bond
- pack together in stable ordered aggregates
- can extend
myristic acid (14:0)
palmitic acid (16:0)
stearic acid (18:0)
unsaturated
- double bond
- cos cannot extend
- greater potential for motion
oleic acid (18:1)
linoleic acid (18:2)
arachidonic acid (20:4)
triacylglycerols
- major energy source for organisms
- most reduced form of carbon [oxidation releases energy]
- no salvation with water [ dehydrated, weighs less]
- efficient packing [van der Waals]
triacylglycerols
if all fatty acids same : simple triacylglycerols
if 2 or 3 different fatty acids : mixed triacylglycerols
conjugation
double bonds can move
glycerophospholipid
A 1,2-diacylglycerol that has a phosphate group esterified at carbon 3 of the glycerol backbone
- if a phospholipid contains a fatty acid with an unsaturation it is usually at the carbon-2 position on the glycerol backbone
glycerophospholipid continued
- phospholipase A1 and A2 cleave fatty acids from a glycerophospholipid producing lysophospholipids
- phospholipase C and D hydrolyze on either side of the phosphate in the polar head group
phospholipids
*play important role as chemical signals in and on cells
- lipid signals act locally
- the lifetime of signals are very short
platelet activating facto [PAF] is an ether glycerophospholipid
- biochemical signaling molecule
1. a potential mediator in inflammation, allergic responses and shock
2. beneficial effect on toxic shock syndrome
3. involved in implantation of the egg in the uterine wall
4. stimulates production of fetal lung surfactant
sphingosines
- found in animal cell membranes
- 18C alcohol, forms backbones of lipids
ceramide
- a fatty acid joined to sphingosine in amide linkage
glycosphingolipids
- ceramics with one or more sugars in beta glycosidic linkage at the 1-hydroxyl group
1 sugar: cerebrosides
3 or more sugars: sialic acid , gangliosides
terpenes
- class of lipids formed from combinations of isoprene units
all steroids
are terpene based molecules
many terpenes are
signaling or regulatory molecules
steroids
isoprene based molecules build on a core structure of 3 6-membered rings and one 5-membered ring, fused together
cholesterol
- the most common steroid in animals and precursor for all other steroids in animals
steroid hormones
serve many functions in animals:
* salt balance
* metabolic function
* sexual function
cortisol
provides control of carbohydrate, protein and lipid metabolism
testosterone
primary male sex steroid hormone
estradiol
primary female sex steroid hormone
progesterone
a precursor of testosterone and estradiol
bile salts/acid [cholic and deoxycholic acid]
- detergent molecules secreted in bile from the gall bladder that assist in the absorption of dietary lipids in the intestine
mass spectromic analysis of white brain matter in early stages of Alzheimers disease
shows a dramatic increase in one type of plasmalogen and 3 fold increase in ceramide levels
functions of membranes
- barrier to toxic molecules
- transport and accumulation of nutrients
- energy transduction
- facilitation of cell motion
- reproduction
- signal transduction
- cell-cell interactions
lipids self associate to form membranes because of the
- hydrophobic effect
- these forces drive the amphiphilic lipids to form membranes
lipids spontaneously form
ordered structures in water
monolayers
on the surface of water arrange lipid tails in the air
micelles
suspended in water bury the non polar tails in the center of the spherical structure
fluid mosaic model
- phospholipid bilayer is a fluid matrix
- 2 dimensional solfent
- lipids and proteins can undergo rotational and lateral movement
fluid mosaic model continued
- lipids can diffuse laterally [rapid]
- transverse motion is slow [ preserves membrane symmetry ]
lipid chain ordering
decreases and motion increases toward the end of the chain, toward the middle of the bilayer
peripheral membrane proteins
- not strongly bound to the membrane
- may form ionic interactions and H bonds with polar lipid head groups or with other proteins
- may interact with non polar membrane core by inserting a short hydrophobic loop or an amphiphilic a-helix
- can be disassociated with high salt concentration
integral membrane proteins
- strongly embedded in lipid bilayer
- can removed by denaturing the membrane with organic solvents or strong detergents
- portions of protein in contact with the non polar core of the bilayer are dominated by a-helices and b-sheets
- neutralize highly polar N-H and C=O functions of the peptide backbone through h bond formation
glycophorin
- integral membrane glycoprotein with a single transmembrane segment
- extracellular portion contains oligosaccharides and these constitute the blood group determinants
- transmembrane protein is a-helical and consists of 19 hydrophobic amino acids
bacteriorhodopsin
- found in purple patches of halo bacterium halobium
- consists of 7 transmembrane helical segments with short loops that interconnect the helices on either side of the membrane
hydropathy plots
- the topology of a membrane protein specifies the number of transmembrane segments and their orientation across the membrane
- segments can be revealed by hydropathy plot
preferred AA locations in transmembrane helices
- the sequence of a transmembrane protein is adapted to the transition from water to the hydrophobic core and then to water
- non polar amino acids are found in hydrocarbon interior
- charged and polar residues occur commonly at the lipid-water interface
- trp, his and try are mixtures of polar and non polar parts [found in lipid water interface]
relative stabilization energies as a function of location in membrane
unfavorable in center: R, D, M, Q, R, K, P
favorable in center: A, G, I, l ,M, F, V
favorable at membrane water interfaces: H, Y, W
why beta barrels?
genetic economy
- a small amount of genetic material can make a large number of transmembrane segments
lipid anchored membrane proteins
- covalently linked to lipids in membrane
- can be reversibly linked to proteins
4 types of lipid anchored proteins
- amide-linked myristoyl anchors
- thirster-linked fatty acyl anchors
- thioether-linked prenyl anchors
- glycosyl phosphatidylionsitol anchors
lipid anchor
always myristic acid (14:0 fatty acid)
always n terminal
a broader specificity for lipids
myristate, palmitate, stearate, and oleate
- always linked to cys
prenylation refers to linking of
“isoprene” based groups
isoprene groups include farnesyl [15C, 3 DB] and geranylgeranyl groups [20C, 4DB]
GPI anchors are more elaborate than others
- ethanol amine link to an oligosaccharide linked in turn to inositol of phosphatidylinositol [PI]
- always attached to a C-terminal carboxyl group of a recognized sequence, GPI linked proteins are found on the cell surface where oligosaccharide links are found
organization and dynamics of membranes
- membranes are asymmetric, heterogeneous structures
- both the lipids and the proteins of the membrane exhibit lateral and transverse asymmetry
lateral asymmetry of proteins
proteins can associate and cluster in the plane of the membrane- they are not uniformly distributed, in many cases
lateral asymmetry of lipids
lipids can cluster in the plane of the membrane- they are not uniformly distributed
transverse asymmetry of proteins
mark Bratscher showed that the N terminus of glycophorin is extracellular whereas C-terminus is intracellular
transverse asymmetry of lipids
in most cell membranes, including those of intracellular organelles, the composition of the outer monolayer is quite different from that of the inner monolayer
proteins that distribute membrane lipids
ATP DEPENDENT:
flipases- move PS from the outer leaflet to inner leaflet “flip in”flopases- move PS form inner leaflet to outer leaflet “flip out” [ cholesterol, pc and sphingomyelin ]
Bi-directional: ca2+ activated but atp dependent
scrambles- randomize lipids across the membrane and thereby degrade membrane lipid symmetry
solid ordered state So
- tightly packed little motion
1. lipid chains are in their fully extended conformation
2. surface area per lipid is minimal
3. bilayer thickness is maximal
liquid disordered state Ld
- more motion
1. lipid chains are more likely to be bent at any one time
2. the surface area per lipid increases
3. bilayer thickness decreases by 10-15%
melting temperature
the transition from gel phase to the liquid crystalline phase is a true phase transition
- the temperature at which this occurs [Tm]
liquid ordered state, Lo
- shows the high lipid ordering of So state and the transitional disorder of the Ld state
- lipid rafts: membranes hypothesized to have Lo phases
- contain large amount of cholesterol, sphingolipids, and GPI-anchored proteins
several ways to induce membrane curvature
- lipid composition
- membrane proteins
- amphipathic helix insertion
- scaffolding
- cytoskeleton
vesicles mediated transport in cells involves
budding of vesicles from a donor membrane, followed by a fusion of the vesicle membrane.
in their fusogenic conformation
viral and cellular fusion proteins pierce and pull membranes together as the proteins refold into alpha-helical bundles between membranes
